Name: SPDPH
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

N-succinimydyl-(3-(2-pyridyldithio)propionate) hexanate; (2,5-dioxopyrrolidin-1-yl) 6-[3-(pyridin-2-yldisulfanyl)propanoylamino]hexanoate;

IUPAC Name

(2,5-dioxopyrrolidin-1-yl) 6-[3-(pyridin-2-yldisulfanyl)propanoylamino]hexanoate

Canonical SMILES

C1CC(=O)N(C1=O)OC(=O)CCCCCNC(=O)CCSSC2=CC=CC=N2

InChI

InChI=1S/C18H23N3O5S2/c22-14(10-13-27-28-15-6-3-5-12-20-15)19-11-4-1-2-7-18(25)26-21-16(23)8-9-17(21)24/h3,5-6,12H,1-2,4,7-11,13H2,(H,19,22)

InChIKey

QYEAAMBIUQLHFQ-UHFFFAOYSA-N

Solubility

In DMSO: 100 mg/mL (235.01 mM; Need ultrasonic)

Appearance

Soild powder

Shipping

Room temperature

Storage

Powder, -20°C, 3 years; 4°C, 2 years; In solvent, -80°C, 6 months; -20°C, 1 month

SPDPH is an effective ADC linker widely employed in antibody-drug conjugate (ADC) development for targeted cancer therapies. As a specialized ADC linker, SPDPH enables stable and site-specific conjugation between monoclonal antibodies and potent ADC cytotoxins, ensuring precise delivery of therapeutic payloads to tumor cells. Its chemical structure allows controlled release of ADC payloads under intracellular conditions, which is a key feature in modern ADC linker design. By integrating SPDPH into ADC constructs, researchers can maintain antibody integrity and antigen-binding specificity while achieving efficient intracellular payload release, enhancing the overall efficacy and safety of ADCs.

SPDPH demonstrates broad compatibility with various ADC cytotoxins, including microtubule-disrupting agents, DNA-targeting drugs, and other potent payloads. Its design supports cleavable linker strategies that respond to specific intracellular conditions, allowing controlled release of cytotoxic agents in tumor cells while reducing systemic toxicity. The chemical stability and predictable reactivity of SPDPH enable high conjugation efficiency, supporting both small-scale research and scalable industrial ADC manufacturing. This versatility makes SPDPH a preferred choice for ADC linker design in preclinical research, drug development, and clinical applications.

From an application perspective, SPDPH-based ADC linkers are widely used in oncology-focused ADC research, bioconjugation studies, and targeted drug delivery systems. Its chemical and enzymatic properties allow researchers to construct modular ADC architectures that optimize tumor specificity, intracellular payload release, and pharmacokinetics. By leveraging SPDPH in ADC linker design, developers can create ADC payload conjugates that exhibit high efficacy, enhanced tumor accumulation, and minimized off-target effects. The linker’s adaptability and compatibility with diverse ADC cytotoxins make it an essential tool in the development of next-generation antibody-drug conjugates.

1. Albumin clusters: structurally defined protein tetramer and oxygen carrier including thirty-two iron(II) porphyrins

Eishun Tsuchida, Teruyuki Komatsu, Akito Nakagawa, Yukiko Oguro Biomacromolecules . 2005 Nov-Dec;6(6):3397-403. doi: 10.1021/bm050454u.

Recombinant human serum albumin (rHSA) clusters have been synthesized and physicochemically characterized. Cross-linking between the Lys groups of the core albumin and a unique Cys-34 of the shell albumins with an N-succinimidyl-6-[3'-(2-pyridyldithio)propionamido]hexanoate produced the structurally defined rHSA trimer and tetramer. MALDI-TOF-MS showed a single peak with the triple and quadruple masses of rHSA. Their molar ellipticities and the isoelectric points (pI = 4.8) are all identical to those of the monomer, suggesting that the essential structures of the albumin units were intact. TEM observations demonstrated a uniform morphology of the rHSA tetramer with a diameter of 20-30 nm. The circulation half-life (tau1/2) of the 125I-labeled rHSA tetramer in rat (5.5 h) was significantly longer than that of the monomer (2.3 h) due to the low ratio of the distribution phase (alpha-phase). A total of 24 and 32 molecules of the synthetic iron(II) porphyrins (FePs) are incorporated into the hydrophobic cavities of the rHSA trimer and tetramer, respectively, producing huge artificial hemoproteins. These albumin-heme clusters can reversibly bind and release O2 under physiological conditions (37 degrees C, pH 7.3) and showed similar O2-binding properties (O2-binding affinity, association and dissociation rate constants) to those of the corresponding monomer. A large volume of O2 can be chemically dissolved into the albumin-heme cluster solutions relative to the monomeric rHSA-FeP when the molar concentration of the albumin scaffold is identical.

2. Purification,characterization and chemical modification studies on a translation inhibitor protein from Luffa cylindrica

Vinod Singh, Anis Alam, Ranjit C Singh Indian J Biochem Biophys . 2003 Feb;40(1):31-9.

A ribosome-inactivating protein (RIP), luffin has been isolated from the seeds of Luffa cylindrica of Cucurbitaceae family by ammonium sulfate fractionation followed by cation exchange and gel-filtration chromatography. Extensive physico-chemical, immunological and biological characterizations were carried out on luffin and compared with that of gelonin. The molecular mass of luffin was -28 kDa as determined by gel-filtration chromatography and SDS-PAGE. The epsilon-NH2 group(s) of luffin were sequentially modified by N-succinimidyl 6-[3-(2-pyridyldithio) propionamido] hexanoate (LC-SPDP), N-succinimidyl-3-(2-pyridylthio)propionate (SPDP) and 2-iminothiolane (2IT) and their effect on immunoreactivity and ribosome inactivating property was evaluated. Modification of single amino group resulted in about 80% inhibition of immunoreactivity and more than 90% loss of protein synthesis inhibition activity. Modification of 2-3 amino groups further hampered both immunoreactivity and protein-synthesis inhibition property LC-SPDP modification played more pronounced effects on immunoreactivity and RIP activity than that of SPDP. However, 2IT modification retained both the immunoreactivity and RIP activity of luffin-LC-SPDP substantially. SPDP showed more pronounced effect on immunoreactivity and RIP activity as compared to 2IT. Therefore, it seems that the positive charge on lysine residues plays an important role in immunological as well as protein synthesis inhibitory effect of luffin.

3. The supramolecular structure of the GPCR rhodopsin in solution and native disc membranes

Dimitrios Fotiadis, Kitaru Suda, Andreas Engel, Krzysztof Palczewski, Slawomir Filipek Mol Membr Biol . 2004 Nov-Dec;21(6):435-46. doi: 10.1080/09687860400020291.

Rhodopsin, the prototypical G-protein-coupled receptor, which is densely packed in the disc membranes of rod outer segments, was proposed to function as a monomer. However, a growing body of evidence indicates dimerization and oligomerization of numerous G-protein-coupled receptors, and atomic force microscopy images revealed rows of rhodopsin dimers in murine disc membranes. In this work we demonstrate by electron microscopy of negatively stained samples, blue native- and sodium dodecyl sulphate-polyacrylamide gel electrophoresis, chemical crosslinking, and by proteolysis that native bovine rhodopsin exists mainly as dimers and higher oligomers. These results corroborate the recent findings from atomic force microscopy and molecular modeling on the supramolecular structure and packing arrangement of murine rhodopsin dimers.

Catalog	Product Name	CAS
BADC-00459	SPDP-PEG8-NHS	1252257-56-9
BADC-00497	sulfo-LC-SPDP	150244-18-1
BADC-00985	Sulfo-SPDP-C6-NHS sodium	169751-10-4
BADC-00011	DM4-SPDP	2245698-48-8
BADC-01092	PC SPDP-NHS carbonate ester	2279944-61-3
BADC-00372	SPDP	68181-17-9
BADC-01315	SPDP-C6-Gly-Leu-NHS ester
BADC-01316	SPDP-PEG12-acid
BADC-01317	SPDP-PEG36-NHS ester

What is SPDPH and its function in ADC linker chemistry?

SPDPH is a heterobifunctional linker containing a hydrazide group and a pyridyldithiol moiety. It enables selective conjugation of antibodies to thiol-containing payloads and allows disulfide-mediated controlled release of the payload in target cells.

9/12/2019

Could you advise how SPDPH enables intracellular payload release?

The pyridyldithiol group forms a disulfide bond with thiol-containing payloads. This bond is stable in systemic circulation but is cleaved under intracellular reducing conditions, releasing the payload specifically inside target cells.

27/5/2019

We are interested in which payloads are compatible with SPDPH.

SPDPH can conjugate cytotoxic small molecules, peptides, or proteins containing free thiols. Its hydrazide group allows coupling to aldehyde-containing payloads, enhancing versatility for ADC synthesis.

6/2/2019

Dear BOC Sciences, what are the recommended conjugation conditions for SPDPH?

Optimal conjugation occurs in slightly basic buffers (pH 7–8) at controlled temperatures. Care is taken to prevent hydrolysis of reactive groups while ensuring efficient formation of disulfide or hydrazone linkages.

5/8/2017

Dear team, how should SPDPH be stored to ensure long-term usability and prevent degradation?

SPDPH should be stored at low temperatures in a tightly sealed container, ideally under inert gas. Light and moisture should be strictly avoided. Proper storage minimizes hydrolysis or oxidation and maintains the functional activity of the linker. Handling instructions and stability data are provided in the accompanying documentation.

7/7/2019

— Dr. Matthew Green, Biochemist (UK)

SPDPH enabled efficient thiol-reactive conjugation with high reproducibility.

6/2/2019

— Ms. Anna Weber, Senior Scientist (Germany)

Lot consistency of SPDPH allowed smooth integration into our ADC synthesis pipeline.

7/7/2019

— Dr. Daniel Clark, ADC Development Scientist (USA)

Using SPDPH, we achieved high conjugation efficiency across multiple batches.

5/8/2017

— Dr. Sophie Laurent, Medicinal Chemist (France)

SPDPH performed reliably in multi-step synthesis, minimizing side products.

9/12/2019

— Mr. Lucas Martin, Research Scientist (Canada)

QC documentation supported regulatory compliance and smooth ADC workflow.

— Dr. Lucas Adams, Biochemist (USA)

SPDPH from BOC Sciences exhibited excellent reactivity and batch-to-batch consistency, making it ideal for our cross-linking studies. Documentation was detailed and clear.

27/5/2019